Chlorotoxin polypeptides and conjugates and uses thereof
Reduced lysine chlorotoxin polypeptides that may be used to generate single species conjugates of chlorotoxin. Conjugates comprising such chlorotoxin polypeptides and pharmaceutical compositions thereof. Methods of using such compositions and/or conjugates.
1. A polypeptide comprising an amino acid sequence having at least 90% sequence identity with SEQ ID NO:1 and comprising no more than one lysine residue.
2. The polypeptide of claim 1 , wherein the polypeptide comprises a single lysine residue, and wherein the single lysine residue is at position 27.
3. The polypeptide of claim 2 , wherein Lys15 and Lys23 are substituted by an amino acid independently selected from the group consisting of natural and unnatural amino acids.
4. The polypeptide of claim 3 , wherein Lys15 and Lys23 are substituted by alanine.
5. The polypeptide of claim 3 , wherein Lys15 and Lys23 are substituted by arginine.
6. The polypeptide of claim 3 , wherein Lys15 is substituted by alanine and Lys23 is substituted by arginine.
7. The polypeptide of claim 3 , wherein Lys15 is substituted by arginine and Lys23 is substituted by alanine.
8. A chlorotoxin conjugate, comprising the polypeptide of claim 1 .
9. The chlorotoxin conjugate of claim 8 , wherein the polypeptide is covalently coupled to one or more of a therapeutic, diagnostic, imaging, or targeting agent.
10. The chlorotoxin conjugate of claim 9 , wherein the polypeptide comprises a single lysine residue, and wherein the therapeutic, diagnostic, imaging, or targeting agent, is covalently coupled to the polypeptide through the single lysine residue.
11. The chlorotoxin conjugate of claim 9 , wherein the diagnostic or imaging agent is selected from the group consisting of a fluorescent label, a radiolabel, and a magnetic resonance imaging label.
12. The chlorotoxin conjugate of claim 9 , wherein the diagnostic or imaging agent is selected from the group consisting of a quantum dot and a polymeric dot.
13. The chlorotoxin conjugate of claim 9 , wherein the diagnostic or imaging agent is selected from the group consisting of a boron nanoparticle, a boron and carbon nanoparticle, and a boron carbide nanoparticle.
14. The chlorotoxin conjugate of claim 9 , wherein the therapeutic agent is selected from the group consisting of methotrexate, docetaxel, cisplatin, etoposide, complementary deoxyribonucleic acid (cDNA), short interfering ribonucleic acid (siRNA), short hairpin ribonucleic acid (shRNA), and an interfering ribonucleic acid (RNA) molecule that mediates ribonucleic acid interference (RNAi).
15. The chlorotoxin conjugate of claim 9 , wherein the diagnostic or imaging agent is selected from the group consisting of a boron-containing polymer, a boron and carbon containing polymer, and a boron carbide polymer.
16. The chlorotoxin conjugate of claim 9 , wherein the imaging agent comprises gadolinium.